Computers from plants we never made. Speculations

We discuss possible designs and prototypes of computing systems that could be based on morphological development of roots, interaction of roots, and analog electrical computation with plants, and plant-derived electronic components. In morphological plant processors data are represented by initial configuration of roots and configurations of sources of attractants and repellents; results of computation are represented by topology of the roots' network. Computation is implemented by the roots following gradients of attractants and repellents, as well as interacting with each other. Problems solvable by plant roots, in principle, include shortest-path, minimum spanning tree, Voronoi diagram, $\alpha$-shapes, convex subdivision of concave polygons. Electrical properties of plants can be modified by loading the plants with functional nanoparticles or coating parts of plants of conductive polymers. Thus, we are in position to make living variable resistors, capacitors, operational amplifiers, multipliers, potentiometers and fixed-function generators. The electrically modified plants can implement summation, integration with respect to time, inversion, multiplication, exponentiation, logarithm, division. Mathematical and engineering problems to be solved can be represented in plant root networks of resistive or reaction elements. Developments in plant-based computing architectures will trigger emergence of a unique community of biologists, electronic engineering and computer scientists working together to produce living electronic devices which future green computers will be made of.Comment: The chapter will be published in "Inspired by Nature. Computing inspired by physics, chemistry and biology. Essays presented to Julian Miller on the occasion of his 60th birthday", Editors: Susan Stepney and Andrew Adamatzky (Springer, 2017

Lung cancer risk among German male uranium miners: a cohort study, 1946–1998

From 1946 to 1990 extensive uranium mining was conducted in the southern parts of the former German Democratic Republic. The overall workforce included several 100 000 individuals. A cohort of 59 001 former male employees of the Wismut Company was established, forming a large retrospective uranium miners' cohort for the time period 1946–1998. Mean duration of follow-up was 30.5 years with a total of 1 801 630 person-years. Loss to follow-up was low at 5.3%. Of the workers, 16 598 (28.1%) died during the study period. Based on 2388 lung cancer deaths, the radon-related lung cancer risk is evaluated. The excess relative risk (ERR) per working level month (WLM) was estimated as 0.21% (95% CI: 0.18–0.24). It was dependent on time since exposure and on attained age. The highest ERR/WLM was observed 15–24 years after exposure and in the youngest age group (<55 years of age). While a strong inverse exposure-rate effect was detected for high exposures, no significant association was detected at exposures below 100 WLM. Excess relative risk /WLM was not modified by duration of exposure. The results would indicate the need to re-estimate the effects of risk modifying factors in current risk models as duration of exposure did not modify the ERR/WLM and there was only a modest decline of ERR/WLM with increasing time since exposure

Celecoxib concentration predicts decrease in prostaglandin E2 concentrations in nipple aspirate fluid from high risk women

<p>Abstract</p> <p>Background</p> <p>Epidemiologic studies suggest that long term low dose celecoxib use significantly lowers breast cancer risk. We previously demonstrated that 400 mg celecoxib taken twice daily for 2 weeks lowered circulating plasma and breast nipple aspirate fluid (NAF) prostaglandin (PG)E₂concentrations in post- but not premenopausal high risk women. We hypothesized that circulating concentrations of celecoxib influenced PGE₂response, and that plasma levels of the drug are influenced by menopausal status. To address these hypotheses, the aims of the study were to determine: 1) if circulating plasma concentrations of celecoxib correlated with the change in plasma or NAF PGE₂concentrations from baseline to end of treatment, and 2) whether menopausal status influenced circulating levels of celecoxib.</p> <p>Methods</p> <p>Matched NAF and plasma were collected from 46 high risk women who were administered celecoxib twice daily for two weeks, 20 subjects receiving 200 mg and 26 subjects 400 mg of the agent. NAF and plasma samples were collected before and 2 weeks after taking celecoxib.</p> <p>Results</p> <p>In women taking 400 mg bid celecoxib, plasma concentrations of the agent correlated inversely with the change in NAF PGE₂levels from pre- to posttreatment. Nonsignificant trends toward higher celecoxib levels were observed in post- compared to premenopausal women. There was a significant decrease in NAF but not plasma PGE₂concentrations in postmenopausal women who took 400 mg celecoxib (p = 0.03).</p> <p>Conclusion</p> <p>In high risk women taking 400 mg celecoxib twice daily, plasma concentrations of celecoxib correlated with downregulation of PGE₂production by breast tissue. Strategies synergistic with celecoxib to downregulate PGE₂are of interest, in order to minimize the celecoxib dose required to have an effect.</p

Application of Direct Renin Inhibition to Chronic Kidney Disease

Chronic kidney disease has serious implications with a high risk for progressive loss of renal function, increased cardiovascular events as well as a substantial financial burden. The renin-angiotensin-aldosterone system (RAAS) is activated in chronic kidney disease, especially in diabetes and hypertension, which are the leading causes of chronic kidney disease. Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) decrease the rate of progression of diabetic and non-diabetic nephropathy and are recommended therapy for chronic kidney disease. Key clinical trials supporting the use of ACE inhibitors and ARBs in chronic kidney disease are discussed. Recent developments in our understanding of RAAS biology and the use of direct renin inhibition are reviewed in the context of their potential impact on the prevention and management of chronic kidney disease. Despite the clinical success of ACE inhibitors and ARBs the rates of mortality and progression to renal failure remain high in these patient populations. ACE inhibitor or ARB monotherapy, in doses commonly used in clinical practice does not result in complete suppression of the RAAS. Aliskiren, a direct renin inhibitor, offers a novel approach to inhibit the RAAS in chronic kidney disease. High dose ARB therapy or combination therapies with ACE inhibitors and ARBs have shown beneficial effects on surrogate markers of chronic kidney disease. Early data based on urinary protein excretion rates as a surrogate marker for renal function suggest a possibly novel role for aliskiren alone or in combination with ARBs in chronic kidney disease

Determinants of persistence in hypertensive patients treated with irbesartan: results of a postmarketing survey

BACKGROUND: Persistence is a key factor for long-term blood pressure control, which is of high prognostic importance for patients at increased cardiovascular risk. Here we present the results of a post-marketing survey including 4769 hypertensive patients treated with irbesartan in 886 general practices in Switzerland. The goal of this survey was to evaluate the tolerance and the blood pressure lowering effect of irbesartan as well as the factors affecting persistence in a large unselected population. METHODS: Prospective observational survey conducted in general practices in all regions of Switzerland. Previously untreated and uncontrolled pre-treated patients were started with a daily dose of 150 mg irbesartan and followed up to 6 months. RESULTS: After an observation time slightly exceeding 4 months, the average reduction in systolic and diastolic blood pressure was 20 (95% confidence interval (CI) -19.6 to -20.7 mmHg) and 12 mmHg (95% CI -11.4 to -12.1 mmHg), respectively. At this time, 26% of patients had a blood pressure < 140/90 mmHg and 60% had a diastolic blood pressure < 90 mmHg. The drug was well tolerated with an incidence of adverse events (dizziness, headaches,...) of 8.0%. In this survey more than 80% of patients were still on irbesartan at 4 month. The most important factors predictive of persistence were the tolerability profile and the ability to achieve a blood pressure target ≤ 140/90 mmHg before visit 2. Patients who switched from a fixed combination treatment tended to discontinue irbesartan more often whereas those who abandoned the previous treatment because of cough (a class side effect of ACE-Inhibitors) were more persistent with irbesartan. CONCLUSION: The results of this survey confirm that irbesartan is effective, well tolerated and well accepted by patients, as indicated by the good persistence. This post-marketing survey also emphasizes the importance of the tolerability profile and of achieving an early control of blood pressure as positive predictors of persistence

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

The response of Plantago major ssp pleiosperma to elevated CO2 is modulated by the formation of secondary shoots

The effect of elevated CO2 on the relative growth rate (RGR) of Plantago major ssp. pleiosperma was studied during the vegetative stage, in relation to plant development, by growing plants at 350 mu l l(-1) or at 700 mu l l(-1) CO2 in non-limiting nutrient solution with nitrate. To minimize interference by the accumulation of non-structural carbohydrates in the interpretation of results, RGR was expressed on a f. wt basis (RGR(FW)), as were all plant weight ratios. Stimulation of the RGR(FW) Of the whole plant by elevated CO2 was transient, and did not last longer than 8 d. At the same time a transient increase in root weight ratio (RWR) was observed. In order to investigate whether the transient effect of elevated CO2 on RGR(FW) was size-dependent, the data were plotted versus total f. wt (log(e) transformed). The transient period of stimulation of RGR(FW) and of RWR by elevated CO2 was still found, but in both CO2 treatments RGR(FW) decreased after a certain plant size had been reached. This size coincided with the stage at which secondary shoots started to develop, and was reached earlier in plants grown at elevated CO2. The RGR of these secondary shoots (RGR(see)) was Still increased when the period of whole plant stimulation of RGR(FW) had ended, indicating that the development of these new sinks took priority over a continuation of the stimulation of RWR. It is hypothesized that in this Plantago subspecies the response of the RGR(FW) of the whole plants to elevated CO2 is modulated by the formation of secondary shoots. Apparently, partitioning of the extra soluble carbohydrates at elevated CO2 to this tissue takes precedence over partitioning to the roots. resulting in a cessation of stimulation of plant RGR(FW) by elevated CO2.info:eu-repo/semantics/publishedVersio